The principle objective of this program is the development of GC-MS methodology for the analysis of selected compounds of biological interest. Some of the highlights of our work to this date are summarized in this space. In a recently published manuscript (Anal. Chem. 49, 1304 (1977)) we have provided a detailed description of the methodology and the overall GC-MS condition required for the analysis of thyroid hormones in serum. The use and value of an isotopically labeled internal carrier for the detection and quantitation of trace levels of T3 and Reverse T3 has been demonstrated. Procedures for the derivatization and GC-MS analysis of apomorphine and its analogs have been established. We have found that O-TMS derivatives provide structurally informative mass spectra, and are thus well suited for the identification of potential metabolic products produced from hydroxylation of the aromatic rings. Isomeric compounds may be distinguished mass spectrometrically on the basis of ions produced from ionically induced interactions of the functional groups in the derived compounds. Mixed N-heptafluorobutyryl-O-TMS derivatives are prepared for the GC-MS analysis of noraporphines, i.e. the N-dealkylated compounds in the series. Preparation of this mixed derivative in noraporphines was promoted by the desirability to retain an O-TMS functionally, and the poor rate of silylation of the secondary amino group at the relatively low (80 degrees C) temperatures employed for derivatization. Due to the thermal sensitivity of the aporphine B-ring the possibility of some thermally induced fragmentations in mass spectrometry is now under investigation.